About MODEYSO
The efficacy and safety of MODEYSO were studied in several clinical trials
About MODEYSO
The efficacy and safety of MODEYSO were studied in several clinical trials
What is MODEYSO?
MODEYSO may alter the process behind H3 K27M–mutant diffuse midline glioma formation
In laboratory studies of H3 K27M–mutant diffuse midline glioma, MODEYSO has been shown to alter the growth and survival of tumor cells
MODEYSO may affect how tumor cells use energy and activate signals that lead to tumor cell death.
MODEYSO may reverse the loss of a chemical marker on histone H3 (trimethylation loss, also called H3 K27me3 loss), which is often disrupted by the H3 K27M mutation.
In cell-based assays and in vivo models of H3 K27M–mutant diffuse glioma, MODEYSO exhibited antitumor activity. Altered mitochondrial metabolism induced by MODEYSO impacts histone demethylases to reverse H3 K27me3 loss2
AKT, protein kinase B; ClpP, caseinolytic protease P; CNS, central nervous system; DRD2, dopamine receptor D2; ERK, extracellular signal-regulated kinase; GPCRs, G protein-coupled receptors; H3, histone 3; RAS, reticular activating system.
MODEYSO results
How MODEYSO was studied in people
The efficacy of MODEYSO was studied in adult and pediatric patients with progressive and measurable H3 K27M–mutant diffuse midline glioma who were previously treated with at least radiation therapy
Prespecified eligibility criteria were designed based on guidance provided by the FDA.
- The first 50 patients who met eligibility for the integrated efficacy analysis were enrolled in the study
- This trial evaluated how many people responded to treatment using special guidelines called RANO 2.0 criteria and how long their responses lasted
FDA, US Food and Drug Administration; RANO, Response Assessment in Neuro-Oncology.
Efficacy results from the MODEYSO clinical trials
Response to treatment
Percentage of patients (11 out of 50) who responded to MODEYSO treatment based on RANO 2.0 criteria
Partial response
16% (8 people) had a partial response, which means the tumor shrank by 50% or more.*
Minor response
6% (3 people) had a minor response, which means the tumor shrank by 25% to 50%.†
Among the 11 people who responded to MODEYSO, the median‡ time to response was 3.6 months.§
How long people responded to MODEYSO||
10.3 months was the median‡ length of time that responses lasted in the 11 people who responded to MODEYSO.
*Applies to enhancing and non-enhancing tumors. In addition, there couldn’t be any new or growing tumors, symptoms had to stay the same or improve, and the patient had to be on the same or a lower dose of steroids.
†Applies only to non-enhancing tumors. There couldn’t be any new or growing tumors, symptoms had to stay the same or improve, and the patient had to be on the same or a lower dose of steroids.
‡Median is the middle number in a group of numbers when arranged from lowest to highest.
§Time to response is the length of time between starting a treatment and seeing a response.
||Duration of response is the length of time from when a tumor begins to respond to treatment until it stops responding or gets worse.
MODEYSO was FDA approved for use based on a pooled analysis of 50 patients that measured how many patients responded and how long they responded. MODEYSO is still being studied to confirm these results.
Individual responses may vary.
MODEYSO safety
Possible side effects with MODEYSO
The safety of MODEYSO was evaluated in 376 adult and pediatric patients with glioma across 4 clinical studies
Most side effects of MODEYSO were mild or moderate in severity.
Heart rhythm problems (QTc interval prolongation)
MODEYSO can cause changes in the electrical activity of your heart and can increase your chance of getting a type of abnormal heart rhythm that can lead to sudden death, a condition called torsades de pointes.
- Before taking MODEYSO, tell your doctor about all your medical conditions, including if you have heart failure or heart rhythm problems, including QT prolongation and long QT syndrome
- Before you start treatment and during treatment as needed, your doctor will check your heart using an electrocardiograph (ECG) and check your blood levels of salts called electrolytes
- Get emergency medical help right away if you get any signs or symptoms of abnormal heart rhythm, including feeling lightheaded or faint, dizziness, fast heartbeat, heart palpitations, or shortness of breath
Allergic reactions
Allergic reactions may happen during treatment with MODEYSO and can be severe.
- Stop taking MODEYSO and get immediate emergency medical help right away if you get any signs or symptoms of allergic reactions, including rash, hives, fever, feeling faint or dizzy, wheezing or trouble breathing, or swelling of the face or throat
Embryo-fetal toxicity
- If you are pregnant or plan to become pregnant, MODEYSO may harm your unborn baby
- Tell your doctor right away if you become pregnant or think that you may be pregnant during treatment with MODEYSO
Around 1 in 3 patients (33%) experienced a serious side effect, which included the following:
- Hydrocephalus, also known as “water on the brain” (5%)
- Vomiting (4%)
- Headache (3%)
- Seizure (2%)
- Muscular weakness (2%)
At least 1 in 5 patients (more than 20%) experienced the following side effects:
FATIGUE
Any grade: 34%
Grade 3 or 4: 3%
HEADACHE
Any grade: 32%
Grade 3 or 4: 4%
VOMITING
Any grade: 24%
Grade 3 or 4: 3%
NAUSEA
Any grade: 24%
Grade 3 or 4: 1%
MUSCULOSKELETAL PAIN
Any grade: 20%
Grade 3 or 4: 3%
In addition to the side effects listed above, at least 1 in 10 patients (more than 10%) experienced the following side effects:
- Difficult walking (gait disturbance)
- Problems with nerves between the brain and parts of the head, face, neck, and torso (cranial nerve disorders)
- Weakness on one side of the body (hemiparesis)
- Slurred speech (dysarthria)
- Dizziness
- Trouble swallowing (dysphagia)
- Muscular weakness
- High blood sugar (hyperglycemia)
- Rash
- Constipation
- Unsteady movements (ataxia)
At least 1 in 10 patients (more than 10%) experienced the following laboratory abnormalities:
- Hemoglobin levels decreased
- White blood cell counts decreased (neutrophils, lymphocytes)
- Liver enzymes increased (alanine aminotransferase, aspartate aminotransferase)
- Electrolyte levels decreased (calcium, sodium, potassium)
- Glucose levels decreased
- Alkaline phosphatase levels increased
Guide to the grades of side effects
Side effects, also known as adverse reactions, are unexpected problems that can happen when someone takes medicine or gets treatment. Side effects receive a grade based on their severity.
- Grade 1, Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated
- Grade 2, Moderate: Minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental ADL
- Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL
- Grade 4: Life-threatening consequences; urgent intervention indicated
- Grade 5: Death related to adverse reaction
Activities of Daily Living (ADL)
Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.
These are not all the possible side effects of MODEYSO. Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
Call your doctor for medical advice about side effects. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1‑800‑FDA‑1088. You may also report side effects to Jazz Pharmaceuticals at 1-866-662-2679.